MicroRNA-29a Compromises Hepatic Adiposis and Gut Dysbiosis in High Fat Diet-Fed Mice via Downregulating Inflammation.

Abstract

miR-29a expression patterns influence numerous physiological phenomena. Of note, upregulation of miR-29a ameliorates high-fat diet (HFD)-induced liver dysfunctions in mice. However, the miR-29a effect on gut microbiome composition and HFD-induced gut microbiota changes during metabolic disturbances remains unclear. We provide compelling evidence for the protective role of miR-29a in gut barrier dysfunction and steatohepatitis. We bred miR-29a overexpressed mice (miR-29aTg) to characterize intestinal, serum biochemical, and fecal microbiota profiling features compared to wild-type mice (WT). Mice were fed an HFD for 8 months to induce steatohepatitis, and intestinal dysfunction was determined via histopathological analysis. miR-29aTg had better lipid metabolism capability that decreased total cholesterol and triglyceride levels in serum than WT of the same age. We further demonstrated that miR-29aTg contributes to intestinal integrity by maintaining periodic acid Schiff positive cell numbers and diversity of fecal microorganisms. HFD-induced bacterial community disturbance and steatohepatitis resulted in more severe WT than miR-29aTg. Gut microorganism profiling revealed Lactobacillus, Ruminiclostridium_9, and Lachnoclostridium enrichment in miR-29aTg and significantly decreased interleukin-6 expression in the liver and intestinal tract. This study provides new evidence that sheds light on the host genetic background of miR-29a, which protects against steatohepatitis and other intestinal disorders. This article is protected by copyright. All rights reserved.